In a study of 114 unrelated VHL families, 85 germline mutations were found. VHL mutations were detected in affected family members, but not in unaffected family members or 96 normal individuals. This mutation also found in 3 family members with VHL type 1 phenotype (family ID 3624), using PCR and SSCP sequencing. The mutation of c.526delA was referred to in the paper by c.739delA due to a difference in transcript sequence. One of 3 individuals was identified with renal cell carcinoma, two with CNS hemangioblastomas and retinal hemngioblastomas. ACMG codes as follows: PVS1, frameshift variant occurs in a gene where loss of function is a known mechanism of disease.

GroupID: 3624

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Familial VHL stated; 3 family members recorded with this mutation.

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0005584 (retinal capillary hemangioma, hemangioblastoma, renal cell carcinoma)

GroupHPOFreeText: 2/3 members had retinal angioma (hemangioma), 2/3 had CNS hemangioblastoma, and 1 had RCC

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 8956040 (type 1 3624NCI)

SupplementalData: N/A

Variant: p.R176Gfs*26 (c.526delA)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.R247fs (c.739delA)

ClinVarID: 625257 https://www.ncbi.nlm.nih.gov/clinvar/variation/625257/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: R176fs (c.526del)

MultipleGeneVariants: N/A

56 male patients age 12 to 76 years, from 40 families with VHL were examined as part of a larger screening program for VHL. VHL mutations were identified in 16 families. Individual patient phenotype-genotype data was not available, but the mutations found and whether the corresponding patient had epididymal cystadenoma (EC) was reported. A c.526delA VHL mutation was found in a VHL patient without EC. This mutation was referred to in the paper as c.739delA due to a difference in transcript sequence.

GroupID: 9

Case: M, Age unknown, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: Unknown

CaseHPOFreeText: Other manifestations may be present although not matched with individuals so could not deduce.

CaseNotHPOs: HP:0009715 (Papillary cystadenoma of the epididymis)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R176Gfs*26 (c.526del)

LegacyVariant: p.R176Gfs*26 (c.739delA)

CaseProblemVariantFreeText: N/A

ClinVarID: 625257 https://www.ncbi.nlm.nih.gov/clinvar/variation/625257/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: Minus_1_frameshift_variant

CivicName: R176Gfs (c.526del)

MultipleGeneVariants: N/A